Abstract
Abstract
Background
Lung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency.
Methods
Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo.
Results
Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects.
Conclusions
Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.
Funder
National Key Research and Development Project of China
Guangdong Basic and Applied Basic Research Foundation
National Natural Science Foundation of China
1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University
the specific research fund of The Innovation Platform for Academicians of Hainan Province
Hainan Province Clinical Medical Center
Publisher
Springer Science and Business Media LLC
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